Ischemic injury of the developing heart.

CARDIAC TOLERANCE TO ISCHEMIA CHANGES SIGNIFICANTLY DURING ONTOGENETIC DEVELOPMENT: the immature heart appears to be more resistant to ischemic injury than the adult myocardium. The mechanisms of the higher tolerance of the developing heart have not yet been satisfactorily clarified; age-dependent changes in energy metabolism have to be taken into consideration. Marked ontogenetic changes are displayed by the mitochondrial membrane potential (MMP): in newborn rats a single population of mitochondria with a relatively high MMP was observed but, with increasing age, the second population with a lower MMP appeared. Adaptation to chronic hypoxia and ischemic preconditioning failed to improve ischemic tolerance of the rat heart on the first postnatal day; the cardioprotective effect only developed at the end of the first postnatal week. Decreasing tolerance of the neonatal heart to ischemia is thus counteracted by the development of endogenous protection. It seems likely that both mitochondrial K(ATP) channels and nitric oxide may be involved in the protective mechanisms of adaptation to chronic hypoxia but not to that of ischemic preconditioning, at least in neonatal rats. Basic knowledge of the possible improvements of immature heart tolerance to ischemia may contribute to the design of therapeutic strategies for both pediatric cardiology and cardiac surgery.